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A new technique has helped researchers find gene switches that could form the basis of new cancer detection techniques and new treatment options.
Scientists have discovered 563,000 DNA switches in 23 types of cancer, including breast (BRCA), skin (SKCM) and lung (MESO, LUAD and LUSC). Credit: M.R.Corces et al./Science 2018
Cellular machinery can only access exposed DNA fragments, not hidden elements in the chromatin. This machine controls which genes are transformed into proteins, using "switches" DNA to activate / deactivate the genes.
Sometimes, however, this switching goes wrong and the genes stay on for too long – or are turned off at the wrong time. Such errors can shake cells and put them on the path to cancer.
The Chang team wanted to list all these DNA switches to better understand all the molecular aberrations related to cancer. Researchers have developed a technology called ATAC-seq (transposase-accessible chromatin assay using sequencing), analogous to spray-painted DNA, explains Chang. The "paint" only highlights the regions accessible to the cellular machines – not the DNA hidden in the chromatin. This gives scientists a way to see exactly which parts of the DNA are active.
ATAC-seq works well on tissue samples, even microscopic, but it was not a guarantee. Years ago, while developing the technology, Chang and his team wanted to modify expensive equipment, a specialized microfluidic station for handling individual cells costing about $ 160,000. The potential reward was high: the ability to "read" chromatin on tumor tissue samples would be a technological breakthrough. But the risk was also the same: tinkering with the material could destroy it completely.
The possibility of this disaster made it difficult to finance Chang's project, he recalls. HHMI, however, tried its luck by allowing the development of technology in 2014.
"This investment was critical," says Chang.
A series of switches
Since 2005, a global consortium of researchers called the Cancer Genome Atlas (TCGA) has been trying to understand the molecular basis of cancer. The work of the consortium has now focused on the discovery of regulatory elements (DNA switches) contributing to the disease.
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